Structural Biochemistry and Mechanisms

Structural Biochemistry and Mechanisms

The recent years of whole genome studies have enforced a view, in which most cellular constituents do not act in isolation, but as part of large assemblies. A large spectrum of biological reactions and tasks essential for the survival of cells are performed by these macromolecular complexes, also referred to as molecular machines. These biochemically labile assemblies are composed of either protein only, or proteins bound to nucleic acids (DNA or RNA). Prominent examples are the proteasome, the fatty acid synthase, the nucleosome, the ribosome, and the spliceosome. As cellular homeostasis is governed by macromolecular complex function, their mis-function is also a central cause for human disease, making the in-depth study of functional mechanisms essential for the investigation of disease etiology.

In our research, we apply mechanistic biochemistry and X-ray crystallography to study large macromolecular complexes involved in proteostasis and fatty acid metabolism. Owing to the labile nature and complexity of interrogating these molecular machines, we are engaged in the development of biochemical tools to purify and stabilize them, as well as arrest them in distinct functional states. We also develop methods for X-ray data collection, phasing, structure determination, and refinement of large complexes. To study dynamic aspects of their function we apply time-resolved approaches.

 

Press Releases & Research News

Elucidating structure with protein chemistry more

A team of researchers, including Ashwin Chari's group from the MPI for Biophysical Chemistry, has identified several candidates for drugs against the SARS-CoV-2 coronavirus. Among them are two promising compounds that are currently being investigated in preclinical studies. This drug screening – probably the largest of its kind – also revealed a new binding site on the virus. more

Holger Stark and his team have broken a crucial resolution barrier in cryo-electron microscopy. The scientists succeeded in observing single atoms in a protein structure and taking the sharpest images ever with this method. Such unprecedented details are essential to understand how proteins perform their work or cause diseases in the living cell. The technique can in future also be used to develop active compounds for new drugs. more

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